Protein‐sulfenic acid stabilization and function in enzyme catalysis and gene regulation

Abstract

Sulfenic acids (R‐SOH) result from the stoichiometric oxidations of thiols with mild oxidants such as H 2 O 2 ; in solution, however, these derivatives accumulate only transiently due to rapid self‐condensation reactions, further oxidations to the sulfinic and/or sulfonic acids, and reactions with nucleophiles such as R‐SH. In contrast, oxidations of cysteinyl side chains in proteins, where disulfide bond formation can be prevented and where the reactivity of the nascent cysteine‐sulfenic acid (Cys‐SOH) can be controlled, have previously been shown to yield stable active‐site Cys‐SOH derivatives of papain and glyceraldehyde‐3‐phosphate dehydrogenase. More recently, however, functional Cys‐SOH residues have been identified in the native oxidized forms of the FAD‐containing NADH peroxidase and NADH oxidase from Streptococcus faecalis ; these two proteins constitute a new class within the flavoprotein disulfide reductase family. In addition, Cys‐SOH derivatives have been suggested to play important roles in redox regulation of the DNA‐binding activities of transcription factors such as Fos and Jun, OxyR, and bovine papillomavirus type 1 E2 protein. Structural inferences for the stabilization of protein‐sulfenic acids, drawn from the refined 2.16‐Å structure of the streptococcal NADH peroxidase, provide a molecular basis for understanding the proposed redox functions of these novel cofactors in both enzyme catalysis and transcriptional regulation.— Claiborne, A., Miller, H., Parsonage, D., Ross, R. P. Protein‐sulfenic acid stabilization and function in enzyme catalysis and gene regulation. FASEB J. 7: 1483‐1490; 1993.